Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity
文献类型：期刊论文
| 作者 | Long, Xuehui1; Zhang, Sulin2; Wang, Yuliang1; Chen, Jingjing1; Lu, Yanlai1; Hou, Hui2; Lin, Bichun1; Li, Xutong2; Shen, Chang2; Yang, Ruirui2 |
| 刊名 | NATURE IMMUNOLOGY
 |
| 出版日期 | 2024-02-14 |
| 页码 | 32 |
| ISSN号 | 1529-2908 |
| DOI | 10.1038/s41590-024-01746-8 |
| 通讯作者 | Zheng, Mingyue(myzheng@simm.ac.cn) ; Qin, Jun(qinjun@sibs.ac.cn) ; Wang, Xiaoming(xmwang@njmu.edu.cn) |
| 英文摘要 | Regulatory T (T-reg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving T-reg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral T-reg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral T-reg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor T-reg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-gamma production and tumor T-reg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral T-reg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor T-reg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor T-reg cells without affecting systemic immune homeostasis. |
| WOS关键词 | NF-KAPPA-B ; STAT3 ; LANDSCAPE ; IDENTITY |
| 资助项目 | National Natural Science Foundation of China (National Science Foundation of China)[32330036] ; National Natural Science Foundation of China (National Science Foundation of China)[T222502] ; National Natural Science Foundation of China (National Science Foundation of China)[81825018] ; National Natural Science Foundation of China (National Science Foundation of China)[82301970] ; National Natural Science Foundation of China (National Science Foundation of China)[82130085] ; National Natural Science Foundation of China (National Science Foundation of China)[82101827] ; National Natural Science Foundation of China (National Science Foundation of China)[82273855] ; National Natural Science Foundation of China (National Science Foundation of China)[82204278] ; National Natural Science Foundation of China (National Science Foundation of China)[31970828] ; National Natural Science Foundation of China[2022YFC3400504] ; National Key Research and Development Program of China[2023296] ; National Key Research and Development Program of China[LG202102-01-02] ; National Key Research and Development Program of China[LG-QS-202204-01] ; Youth Innovation Promotion Association CAS[2022M721675] ; Youth Innovation Promotion Association CAS[2020M681665] ; Youth Innovation Promotion Association CAS[2022M720153] ; China Postdoctoral Science Foundation[KYCX22_1784] ; China Postdoctoral Science Foundation[JX10113833] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province[TZBSHKY202203] ; Postdoc Research Program of Taizhou School of Clinical Medicine[WMCM202310] ; Major Program of Wuxi Medical Center, Nanjing Medical University[BE2022770] ; Jiangsu Provincial Key Research Development Program of China[BK20200030] ; Jiangsu Outstanding Young Investigator Program |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| WOS记录号 | WOS:001162638000005 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309599]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zheng, Mingyue; Qin, Jun; Wang, Xiaoming |
| 作者单位 | 1.Nanjing Med Univ, Wuxi Peoples Hosp, Affiliated Taizhou Peoples Hosp, Affiliated Wuxi Peoples Hosp,Collaborat Innovat Ct, Nanjing, Peoples R China 2.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr,State Key Lab Drug Res, Shanghai, Peoples R China 3.Nanjing Med Univ, Affiliated Wuxi Peoples Hosp, Wuxi Peoples Hosp, Wuxi Med Ctr,Dept Lab Med, Wuxi, Peoples R China 4.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Ctr Excellence Mol Cell Sci,CAS Key Lab Tissue, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Long, Xuehui,Zhang, Sulin,Wang, Yuliang,et al. Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity[J]. NATURE IMMUNOLOGY,2024:32. |
| APA | Long, Xuehui.,Zhang, Sulin.,Wang, Yuliang.,Chen, Jingjing.,Lu, Yanlai.,...&Wang, Xiaoming.(2024).Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity.NATURE IMMUNOLOGY,32. |
| MLA | Long, Xuehui,et al."Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity".NATURE IMMUNOLOGY (2024):32. |
入库方式： OAI收割
来源：上海药物研究所
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